Neurotoxicity resulting from industrial exposure to the solvent n-hexane and its related chemicals (hexacarbons) has been recently documented in many countries, including the United States. Also, for many years organophosphorus esters have been recognized as the causitive agents to major breakout incidents of neuropathy in humans. Neurotoxicity resulting from these two classes of chemicals has been studied in separate species--hexacarbon neurotoxicity mostly in rats and organophosphorus neurotoxicity mostly in chickens. A major concern in industry and in regulatory agencies is the possibility that workers may be exposed to both classes of neurotoxicants at the same time. In fact, simultaneous exposure of workers to n-hexane and the neurotoxic insecticide leptophos had occurred. The key goal of this proposal is to study the interaction between neurotoxicity induced by hexacarbons and organophosphorus esters in a sensitive species (the hen). This includes the sensitivity of the chicken to neurotoxicity induced by n-hexane and related chemicals and the characterization and distribution of the histopathologic lesions in the nerve tissues of chickens. These results are to be compared to those obtained from the organophosphorus insecticide EPN (0-ethyl 0-4-nitrophenyl phenylphosphonothioate). The effect of the combined exposure to the hexacarbons and EPN on developing neurotoxicity in the hen is to be investigated. Exposure to hexacarbon solvents will be via inhalation, oral, dermal or peritoneal injection. EPN will be dermally applied for 90 days. The effect of hexacarbons on the pharmacokinetics and metabolism of (14C)EPN will be studied. The change of enzymatic activities of brain and plasma cholinesterase and of hepatic cytochrome P-450 as the result of these treatments will be determined.